Autoreceptor-induced inhibition of neuropeptide Y release from PC-12 cells is mediated by Y-2 receptors
Autoreceptor-induced inhibition of neuropeptide Y release from PC-12 cells is mediated by Y-2 receptors
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DOI：
10.1152/ajpheart.1997.273.4.h1737
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发表时间：
1997-10-01
影响因子：
4.8
通讯作者：
Westfall, TC
中科院分区：
文献类型：
--
作者：
Chen, XL;DiMaggio, DA;Westfall, TC
当用神经生长因子（NGF）分化时，嗜铬细胞瘤（PC）-12细胞表达Y-1、Y-2和Y-3神经肽Y（NPY）受体。本工作评估了NGF分化的PC-12细胞作为模型系统来研究NPY自身受体对NPY释放的调节。我们证明，K+和尼古丁刺激从分化的PC-12细胞的NPY和多巴胺的伴随释放。本研究还表明，Y-2型NPY受体的选择性激动剂肽YY（PYY）-（13-36）以浓度依赖性方式减弱PC-12细胞的NPY释放。这一结果表明，Y-2亚型的NPY自身受体可以调节NPY的释放。PYY-（13-36）的抑制作用可能至少部分通过抑制N型Ca 2+通道来介导，因为PYY-（13-36）在最大有效浓度的ω-芋螺毒素（一种N型Ca 2+通道阻断剂）存在下不能产生进一步的抑制作用。PYY-（13-36）的抑制作用可被百日咳毒素预处理的细胞所阻断，提示抑制性GTP结合蛋白参与了抑制作用。此外，NPY自身受体的功能可以通过其他受体如β-肾上腺素能受体和ATP受体来调节。诱发释放的NPY也被ATP和腺苷减弱，这已被证明是共定位和共释放的交感神经末梢的NPY。这些结果表明，PC-12细胞与NGF分化可能是一个理想的模型，以研究NPY释放的调节机制和自身受体介导的调节NPY的释放似乎是通过Y-2亚型的NPY受体。
Pheochromocytoma (PC)-12 cells express Y-1, Y-2, and Y-3 neuropeptide Y (NPY) receptors when differentiated with nerve growth factor (NGF). The present work evaluated NGF-differentiated PC-12 cells as a model system to study modulation of NPY release by NPY autoreceptors. We demonstrated that both K+ and nicotine stimulated concomitant release of NPY and dopamine from differentiated PC-12 cells. We also showed in this study that NPY release from PC-12 cells was attenuated in a concentration-dependent manner by peptide YY (PYY)-(13-36), a selective agonist for the Y-2 type of NPY receptors. This result demonstrated that NPY release could be modulated by NPY autoreceptors of the Y-2 subtype. The inhibitory action of PYY-(13-36) may be mediated at least in part by inhibition of N-type Ca2+ channels, because PYY-(13-36) could not produce further inhibitory effects in the presence of a maximum effective concentration of omega-conotoxin, an N-type Ca2+-channel blocker. The inhibition by PYY-(13-36) could be blocked by pretreatment of cells with pertussis toxin, suggesting that an inhibitory GTP-binding protein was involved. Furthermore, the function of NPY autoreceptors could be modulated by other receptors such as beta-adrenergic and ATP receptors. The evoked release of NPY was also attenuated by ATP and adenosine, which have been shown to be colocalized and coreleased with NPY from sympathetic nerve terminals. These results suggest that PC-12 cells differentiated with NGF may be an ideal model to study regulatory mechanisms of NPY release and that autoreceptor-mediated regulation of NPY release appears to act through the Y-2 subtype of the NPY receptor.